Non-Small Cell Lung Cancer MedDRA version: 14.1 Level: LLT Classification code 10025054 Term: Lung cancer non-small cell stage IIIB System Organ Class: 100000004864 MedDRA version: 14.1 Level: LLT Classification code 10025055 Term: Lung cancer non-small cell stage IV System Organ Class: 100000004864
Conditions
Sponsors
Synta Pharmaceuticals Corp.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female subjects aged 18 years or older 2. Pathologically confirmed (by histology or cytology) diagnosis of NSCLC with predominantly adenocarcinoma histology 3. Stage IIIB or IV NSCLC according to the AJCC Cancer Staging Manual 7th Edition 2010 4. ECOG Performance Status 0 or 1 and life expectancy of at least 3 months at screening 5. Eligible for second-line systemic therapy: •Patients must have received no more than one prior therapy (first-line therapy) for advanced disease (Stage IIIB or IV). Prior first-line therapy may include: i. A platinum-based chemotherapy doublet (with or without biological agents); or ii. EGFR tyrosine kinase inhibitors (TKIs) for EGFR-mutated disease •NOTE: Maintenance therapy following first-line treatment for advanced disease is allowed, as long as it was started no more than 4 weeks after the last dose of first-line therapy •NOTE: Previous anticancer treatment must have stopped at least 2 weeks prior to randomization 6. Measurable disease by modified RECIST 1.1 7. Radiologic evidence of primary or secondary disease progression following first-line treatment. Disease progression is defined as: •Appearance of any new lesion or any measureable increase of one or more existing lesions. Radiological scans or radiology reports from the subject’s most recent treatment must document the baseline or lowest tumor burden (nadir scans) and disease progression. NOTE: Disease progression is defined either as a primary progression where a patient never responded to first line treatment; or secondary progression, where disease progression occurred after initial response 8. Subjects with CNS metastases are eligible, provided that the CNS metastases are radiologically and clinically stable for at least 4 weeks after appropriate therapy (with or without steroid treatment) prior to randomization 9. Adequate hematologic function defined as: • Absolute neutrophil count (ANC) = 1.5 × 109/L • Hemoglobin = 9 g/dL • Platelets = 100 × 109/L 10. Adequate hepatic function defined as: • Albumin =3 g/dL • Serum total bilirubin =1.5 x ULN • AST and ALT =1.5 × ULN without liver metastases; =5 × ULN if documented liver metastases 11. Adequate renal function defined as • Serum Creatinine =1.2 mg/dL or calculated creatinine clearance (CLcr) per Cockgroft- Gault formula = 50mL/min 12. Negative serum pregnancy test at study entry for female subjects of childbearing potential 13. Female subjects of childbearing potential and males must agree to use adequate contraception (e.g., hormonal or barrier method of birth control; abstinence) for the duration of study treatment and for 30 days after the last dose of study drug. 14. Ability to understand, and willingness to sign, a written informed consent document and to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures 15. Translational Research: archived or newly obtained tumor tissue, consisting of at least 10 unstained slides or a block of fixed tumor tissue, must be coll
Exclusion criteria
Exclusion criteria: 1. Presence of active or untreated CNS metastases as determined by MRI or CT scan performed during screening. 2. Active malignancies other than NSCLC within the last 5 years with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri or basal or squamous cell carcinoma of the skin 3. Serious cardiac illness or medical conditions including but not confined to: • History of documented congestive heart failure (CHF), New York Heart Association class II/III/IV, with a history of dyspnea, orthopnea or edema that requires current treatment with angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers or diuretics. NOTE: Use of these medications for the treatment of hypertension is allowed • Baseline QTc > 470 msec or history of QT prolongation while taking other medications • High-risk uncontrolled arrhythmias (ventricular tachycardia, high-Grade AV-block, supra-ventricular arrhythmias which are not adequately rate-controlled) that require current treatment with the following anti-arrythmic drugs: flecainide, moricizine or propafenone • Current coronary artery disease with a history of myocardial infarction, angina pectoris, angioplasty or coronary bypass surgery 4. Radiotherapy within 2 weeks prior to randomization (related toxicities must be =Grade 1) 5. Prior radiotherapy to the only area of measurable disease 6. Major surgery (unrelated to NSCLC) within 4 weeks prior to randomization 7. Hemoptysis = Grade 2 at randomization 8. Peripheral neuropathy = Grade 2 at randomization 9. History of severe allergic or hypersensitivity reactions to docetaxel or excipients (eg, polyethylene glycol [PEG] 300 and polysorbate 80) 10. Women who are pregnant or lactating 11. Significant weight loss of = 10% body weight within the 4 weeks prior to randomization
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Stage 1 Evaluate progression free survival (PFS) in subjects with NSCLC with adenocarcinoma histology who present with elevated baseline total LDH treated with the combination of ganetespib and docetaxel compared to docetaxel alone. Evaluate PFS in subjects with KRAS mutated NSCLC. Stage 2 Assess OS in subjects with stage IIIB or IV NSCLC treated with the combination of ganetespib and docetaxel compared to docetaxel alone ; Secondary Objective: Stage 1 •Evaluate the PFS & OS in subjects with NSCLC with adenocarcinoma histology •Compare the two treatments in subjects with elevated baseline serum levels of total LDH with respect to the following: Overall Response Rate (ORR), Disease Control Rate (DCR), tumor size change, 1-year OS rate, and OS •Compare the two treatments in subjects with mutated KRAS (mKRAS) with respect to the following: ORR, DCR, tumor size change, 1-year OS rate, and OS •Compare the two treatment groups in the adeno population with respect to the following: ORR, DCR, tumor size change and 1-year OS rate •Compare the two treatment groups with respect to other important pre-specified prognostic factors according to the following: PFS, ORR, DCR, tumor size change, 1-year OS rate, and OS Stage 2 1. Compare the two treatment groups with respect to the following: PFS, ORR, DCR, tumor size change and 1-year OS ; Primary end point(s): Stage 1 The primary endpoints of the study are (1) PFS in adenocarcinoma histology subjects with elevated baseline total LDH and (2) PFS in a subset of subjects with KRAS mutated disease. Stage 2 Evaluation of OS in the two treatment arms ; Timepoint(s) of evaluation of this end point: Stage 1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Stage 1 Overall Response Rate, Disease Control Rate, tumour size change, and 1 year overall survival and overall survival between the 2 treatment groups. Stage 2 Progression Free Survival, Overall Response Rate, Disease Control Rate, tumour size changes, and 1 year overall survival and overall survival between the 2 treatment groups ; Timepoint(s) of evaluation of this end point: Stage 1 and Stage 2 Tumor size changes from baseline to at least 6 or 12 weeks Disease Control Rate is defined as the proportion of patients with best response, according to modified RECIST 1.1, of CR, PR or SD, where the SD must be for at least 6 weeks (DCR-6) or 12 weeks (DCR-12) | — |
Countries
Belgium, Bosnia and Herzegovina, Canada, Croatia, Czech Republic, Germany, Hungary, Netherlands, Poland, Romania, Russian Federation, Serbia, Spain, Ukraine, United Kingdom, United States
Contacts
Public ContactSenior Clinical Trials Manager
Synta Pharmaceuticals Corp.
Outcome results
None listed